Steroid hormones partition to distinct sites in a model membrane bilayer: direct demonstration by small-angle X-ray diffraction.
The classical, genomic mechanisms of steroid hormone action cannot account for their rapid cellular effects. Membrane-bound steroid receptors have been partially characterized, but many rapid steroid effects occur in the absence of steroid-protein binding. Although it has been proposed that these effects could be due to steroid-induced biophysical alterations of the cell membrane, only indirect supporting evidence for this hypothesis has been forthcoming. In the present study, the ability of cortisol and estradiol (E2), natural steroids of different lipophilicity, to induce alterations in a model membrane (lecithin) bilayer was examined directly by small-angle X-ray diffraction under physiologic-like conditions. Within minutes, both steroids partitioned to distinct sites in the membrane. With increasing membrane cholesterol content, cortisol was displaced toward the polar headgroup region of the phospholipid bilayer, whereas E2 was displaced in the opposite direction, toward the nonpolar hydrocarbon core. Membrane-based partition coefficients (Kp[mem]) for both steroids (>100:1) were highest at those cholesterol concentrations that displaced the steroids toward the headgroup region (high cholesterol for cortisol; low for E2). Both steroids, when located in the headgroup region, increased overall bilayer width by 3-4 A, a change that could modulate the structure and function of integral membrane proteins independent from steroid effects on the genome.
Golden
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Center for Neurosciences Research, MCP, Hahnemann School of Medicine, Allegheny University of the Health Sciences, Pittsburgh, PA 15212, USA.
Rubin
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Mason
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D002784:Cholesterol; D004958:Estradiol / Q000737:chemistry*; D006854:Hydrocortisone / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D010713:Phosphatidylcholines; D014961:X-Ray Diffraction / Q000379:methods
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D004958:Estradiol; D002784:Cholesterol; D006854:Hydrocortisone